Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study

Abstract

INTRODUCTIONLittle is known about the heterogeneous treatment effects of metformin on dementia risk in people with type 2 diabetes (T2D).METHODSParticipants (≥ 50 years) with T2D and normal cognition at baseline were identified from the National Alzheimer's Coordinating Center database (2005–2021). We applied a doubly robust learning approach to estimate risk differences (RD) with a 95% confidence interval (CI) for dementia risk between metformin use and no use in the overall population and subgroups identified through a decision tree model.RESULTSAmong 1393 participants, 104 developed dementia over a 4‐year median follow‐up. Metformin was significantly associated with a lower risk of dementia in the overall population (RD, –3.2%; 95% CI, –6.2% to –0.2%). We identified four subgroups with varied risks for dementia, defined by neuropsychiatric disorders, non‐steroidal anti‐inflammatory drugs, and antidepressant use.DISCUSSIONMetformin use was significantly associated with a lower risk of dementia in individuals with T2D, with significant variability among subgroups.

Current type 2 diabetes guidelines: Individualized treatment and how to make the most of metformin

“…100 However, current evidence on the attenuated risk of dementia with metformin use remains inconclusive. 101,102 Although some studies suggested that metformin might reduce the risk of dementia and improve cognition in patients with diabetes, the results were limited by small sample sizes and inadequate adjustment for confounding factors. On the other hand, some researchers reported an increased risk of dementia with metformin.…”

“…This might lead to subclinical deficiency, which contributes to cognitive decline. 104,105 Although the effects of metformin on cognitive function might depend on the dose and treatment duration, 102 there are limited interventional studies investigating the effects of metformin and its relationships with vitamin B12 on cognitive function. 52…”